Many diseases affect kidney function by attacking the glomeruli, the tiny clusters of capillaries within the kidney that filter blood and remove fluid and waste products from the body in the form of urine. Diseases affecting the glomeruli include conditions with a variety of genetic and environmental causes that broadly fall within two classes: glomerulonephritis and glomerulosclerosis. Glomerulonephritis refers to inflammation of the membrane tissue in the kidney that serves as a filter, separating wastes and extra fluid from the blood. Glomerulosclerosis refers to the scarring or hardening of the glomeruli. Such scarring is typically caused by the activation of podocytes by growth factors produced by the podocytes themselves or brought to the glomerulus by circulating blood. Glomerulosclerosis may present as focal segmental glomerulosclerosis, diffuse glomerulosclerosis, nodular glomerulosclerosis, or intercapillary glomerulosclerosis. Subjects with focal segmental glomerulosclerosis (FSGS) exhibit scarring in scattered regions of the kidney that is typically limited to one part of the glomerulus and to a minority of glomeruli in the affected region. FSGS may result from a systemic disorder such as hypertension or obesity, or it may develop as an idiopathic disease. There are various subtypes of FSGS, including˜primary (idiopathic or sporadic), secondary, familial, and FSGS associated with congenital syndromes.
Diagnosis of FSGS is typically based on histopathologic findings following renal biopsy, although the glomerular pathology may result from multiple different molecular or cellular processes and be unrelated to a particular disease. A characteristic feature of FSGS is proteinuria, a condition in which urine contains an abnormal amount of protein, which suggests that FSGS involves a loss or reduction of the filtration barrier between the glomerular filter and the urinary space. Since the pathophysiology of FSGS is poorly understood, the disease remains difficult to treat. In the absence of a “universal” treatment regimen for FSGS, many subjects progress to end-stage renal disease (ESRD) within 5 to 20 years. Subjects with particularly aggressive FSGS may reach ESRD within 2 to 3 years of diagnosis.
Due to the severity of symptoms associated with FSGS and the potential to progress to end-stage renal disease, there remains a need to more conclusively identify individuals at risk for developing kidney diseases and to select and optimize appropriate therapies based on an individual's genotypic subtype.